Although it is now generally recognized that a properly functioning thymus gland is necessary for both the development and maintenance of cell-mediated immunity, the mechanisms by which these are accomplished are poorly characterized. The impetus for the proposed study is based upon the recent purification to homogeneity of thymosin, a thymic hormone which was isolated and purified in our laboratory from calf thymus tissue. A second impetus is the demonstration thatthis humoral factor circulates in the blood and can partially replace thymic function in neonatally thymectomized mice. The proposed research has the following objectives: (1) to elucidate the endocrine role of the thymus gland in relation to aging process in the lymphoid system, including both the oncogenesis and senescence of the immune response; (2) to determine the role of thymosin and an anti-thymosin serum in the etiology of diseases characterized by hyper- or hypothymic function; and (3) to characterize completely the structure(s) and mechanism of action of bovine and human thymosin. Experimental approaches will include: (1) development and clinical application of a radioimmunoassy for human thymosin; (2) evaluation of thymosin-treated lymphocyte populations from normal, aged, or immunosuppressed mice as well as mice with autoimmune diseases, leukemia, and virus-induced neoplasms; (3) determination of the amino acid sequence of bovine and human thymosin; and (4) localization, and characterization of the thymosin receptor. BIBLIOGRAPHIC REFERENCES: Wara, D.W., Goldstein, A.L., Doyle, W. and Ammann, A.J. 1975. Thymosin Activity in Patients with Cellular Immunodeficiency. New Eng. J. of Med., 292, 70; Markham, R.B., White, A. and Goldstein, A.L. 1975. Selective Immunosuppressive Activity of Steroids in Mice Inoculated with the Moloney Sarcoma Virus. Proc. Soc. Exp. Biol. & Med. 148, 190.